Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases

Abstract

IMPORTANCEPatients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM.OBJECTIVE To compare clinical outcomes in patients with BM treated with etirinotecan pegol vs chemotherapy of the physician's choice in a confirmatory trial. DESIGN, SETTING, AND PARTICIPANTSThis study was a phase 3, open-label, randomized clinical trial (ATTAIN) in patients with metastatic breast cancer and a history of stable pretreated BM who experienced disease progression while receiving chemotherapy in the metastatic setting. The trial took place at 47 sites in 10 countries, and patients were enrolled between March 7, 2017, and November 6, 2019.INTERVENTIONS Patients were randomized to receive etirinotecan pegol, 145 mg/m 2 , every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). MAIN OUTCOMES AND MEASURESThe primary end point was OS. Key secondary end points included progression-free survival, objective response rate, duration of response, and the clinical benefit rate. RESULTS A total of 178 female patients (9 [5.1%] Asian, 8 [4.5%] Black or African American, and 123 [69.1] White individuals) were randomized to receive treatment with etirinotecan pegol (92 [51.7%]; median [range] age, 53 [27-79] years) or chemotherapy (86 [48.3%]; median [range] age, 52 [24-77] years). Median OS was similar in both groups (etirinotecan pegol, 7.8 months; chemotherapy, 7.5 months; hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P = .60). Median progression-free survival for non-central nervous system metastases per blinded independent central review for etirinotecan pegol vs chemotherapy was 2.8 and 1.9 months (HR, 0.72; 95% CI, 0.45-1.16; P = .18) and 3.9 vs 3.3 months, respectively, for central nervous system metastases (HR, 0.59; 95% CI, 0.33-1.05; P = .07). Safety profiles between the groups were largely comparable. CONCLUSIONS AND RELEVANCEThe results of the ATTAIN randomized clinical trial found no statistically significant difference in outcomes between treatment with etirinotecan pegol and chemotherapy in patients with BM. However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research.

Systemic treatments for breast cancer brain metastasis

“…In the BEACON trial (a phase III trial), BCBM patients who received NKTR-102 treatment had a markedly lowered death risk than those who received treatment of physician's choice (TPC) (HR 0.51; P < 0.01), with median OS of 10.0 and 4.8 months, respectively (81). In ATTAIN trial, a phase III study of NKTR 102 versus TPC in metastatic BC patients (82), the median PFS in BM patients of NKTR 102 and TPC was 3.9 and 3.3 months, respectively (HR, 0.59; 95% CI, 0.33-1.05; P =0.07), and the median OS in both the groups was nearly the same (7.8 months for NKTR 102, and 7.5 months for TPC group; HR=0.90; 95% CI, 0.61-1.33; P =0 .60) (83). The ATTAIN randomized clinical trial was not consistent with the positive OS benefit observed in BEACON trial (81,83).…”

“…In ATTAIN trial, a phase III study of NKTR 102 versus TPC in metastatic BC patients (82), the median PFS in BM patients of NKTR 102 and TPC was 3.9 and 3.3 months, respectively (HR, 0.59; 95% CI, 0.33-1.05; P =0.07), and the median OS in both the groups was nearly the same (7.8 months for NKTR 102, and 7.5 months for TPC group; HR=0.90; 95% CI, 0.61-1.33; P =0 .60) (83). The ATTAIN randomized clinical trial was not consistent with the positive OS benefit observed in BEACON trial (81,83).…”

Targeting Breast Cancer: An Overlook on Current Strategies

“…Etirinotecan pegol (NKTR-102) is a long-acting topoisomerase-I inhibitor used for patients with MBC and brain metastases. However, in the phase III ATTAIN randomized clinical trial, no statistically significant difference in survival outcomes was observed in patients treated with etirinotecan pegol and patients treated with chemotherapy of physician’s choice [ 147 ]. These findings are questionable [ 148 ] and further studies are needed.…”

Etirinotecan Pegol Treatment for Patients With Metastatic Breast Cancer and Brain Metastases

“…To the Editor We read with interest the article by Tripathy et al reporting the results of the ATTAIN randomized clinical trial, which found no statistically significant difference in survival outcomes between treatment with etirinotecan pegol (EP) and chemotherapy of physician’s choice (CPC) in patients with breast cancer with brain metastases. Although this study is impressive, we have a few concerns and suggestions for this study.…”

“…This study did not compare the size, number, and location of brain metastases between the 2 groups to control confounding factors. This study also did not report the comparison of objective response rate (ORR) between the EP and CPC groups.…”